丹参注射液联合消瘤颗粒对子宫肌瘤大鼠激素水平的影响及机制研究

目的探讨丹参注射液联合消瘤颗粒对子宫肌瘤大鼠激素水平的影响,并分析其机制。方法以30只成年雌性未孕无特定病原体级SD大鼠为研究对象,采用苯甲酸雌二醇联合黄体酮肌注建立子宫肌瘤模型,并按照随机数字表法分为4组:模型对照组(n=7),腹腔注射和灌胃等量0.9%氯化钠溶液、治疗A组(n=7),腹腔注射1 mL丹参注射液+等量0.9%氯化钠溶液灌胃、治疗B组(n=8),腹腔注射等量0.9%氯化钠溶液+5 g/kg消瘤颗粒悬浊液灌胃和治疗A+B组(n=8),腹腔注射1 mL丹参注射液+5 g/kg消瘤颗粒悬浊液灌胃治疗。分别于治疗前、治疗后7 d、治疗后15 d及治疗后30 d清晨空腹状态下,对各组大鼠进行称重并记录;治疗结束后,取各组大鼠称重并计算各组子宫系数,采用放射免疫分析法试剂盒检测各组大鼠血清和子宫组织匀浆中雌二醇(E2)和孕激素(P)水平,采用蛋白质印迹法检测子宫组织匀浆中胰岛素样生长因子结合蛋白-3(IGFBP-3)和血管内皮生长因子(VEGF)相对表达。结果治疗后15 d,与模型对照组相比,治疗A+B组大鼠体重显著增加,差异有统计学意义(P<0.05);治疗后30 d,与模型对照组相比,其余3组大鼠体重均显著降低,治疗A+B组也显著低于治疗A组和治疗B组,差异均有统计学意义(P<0.05)。与模型对照组相比,其余3组大鼠子宫重量和子宫系数均显著降低,治疗A+B组也显著低于治疗A组和治疗B组,差异均有统计学意义(P<0.05)。与模型对照组相比,其余3组大鼠血清和子宫组织中雌二醇和孕激素含量均显著升高,治疗A+B组也显著高于治疗A组和治疗B组,差异均有统计学意义(P<0.05)。与模型对照组相比,其余3组大鼠子宫组织中IGFBP-3相对表达量均显著升高,VEGF相对表达量则显著降低,治疗A+B组IGFBP-3相对表达量显著高于治疗A组和治疗B组,VEGF相对表达量则显著低于治疗A组和治疗B组,差异均有统计学意义(P<0.05)。结论丹参注射液联合消瘤颗粒对子宫肌瘤具有显著消瘤效果,可促进大鼠血清及子宫组织中激素水平的恢复,其作用机制可能与调控大鼠IGFBP-3和VEGF蛋白表达有关,并且伴随着治疗作用的进一步增强,大鼠子宫肌瘤组织中IGFBP-3表达显著增加,VEGF表达显著降低。

Effects and mechanism of Danshen injection combined with Xiaoliu granules on hormone levels in rats with uterine fibroids

Objective To investigate the effect of Danshen injection combined with Xiaoliu granules on hormone levels in rats with uterine fibroids,and analyze its mechanism.Methods Thirty adult female non-pregnant specific pathogen free SD rats were taken as the research object,intramuscular injection of estradiol benzoate and progesterone was used to establish a uterine fibroids model.According to the random number table method,they were divided into 4 groups:model control group(n=7),intraperitoneal injection and gavage of the same amount of normal saline),treatment group A(n=7),intraperitoneal injection of 1 mL of Danshen injection+equal amount of normal saline by gavage),treatment group B(n=8),intraperitoneal injection of the same amount of normal saline+5 g/kg Xiaoliu granule suspension liquid by gavage)and treatment group A+B(n=8),intraperitoneal injection of 1 mL of Danshen injection+5 g/kg Xiaoliu granule suspension for intragastric treatment).Before treatment,7 days after treatment,15 days after treatment,and 30 days after treatment,the rats in each group were weighed and recorded in the early morning.After the treatment,the rats in each group were weighed and the uterine coefficient of each group was calculated.The radioimmunoassay kit was used to detect the levels of estradiol(E2)and progesterone(P)in the serum and uterine tissue homogenate of each group of rats.Western blotting was used to detect the relative expression of insulin-like growth factor binding protein-3(IGFBP-3)and vascular endothelial growth factor(VEGF)in uterine tissue homogenate.Results 15 days after treatment,compared with the model control group,the weight of rats in the treatment A+B group increased significantly,the difference was statistically significant(P<0.05);30 days after treatment,compared with the model control group,the weight of the rats in the other three groups was significantly reduced,and the treatment A+B group was also significantly lower than that in the treatment A group and the treatment B group,the differences were statistically significant(P<0.05).Compared with the model control group,the uterine weight and uterine coefficient of the other three groups were significantly reduced,and the treatment A+B group was also significantly lower than the treatment A group and the treatment B group,the differences were statistically significant(P<0.05).Compared with the model control group,the contents of estradiol and progesterone in the serum and uterine tissue of the other three groups of rats were significantly increased,and the treatment A+B group was also significantly higher than the treatment A group and the treatment B group,the differences were statistically significant(P<0.05).Compared with the model control group,the relative expression of IGFBP-3 in the uterine tissues of the other three groups was significantly increased,while the relative expression of VEGF was significantly reduced.The relative expression of IGFBP-3 in the treatment A+B group was significantly higher than that in the treatment A and B groups,and the relative expression of VEGF was significantly lower than that in the treatment A and B groups,the differences were statistically significant(P<0.05).Conclusion Danshen injection combined with Xiaoliu granules has a significant antitumor effect on uterine fibroids and can promote the recovery of hormone levels in rat serum and uterine tissue.Its mechanism of action may be related to the regulation of the expression of IGFBP-3 and VEGF protein in rats.And with the further enhancement of the therapeutic effect,the expression of IGFBP-3 in rat uterine fibroids increased significantly,and the expression of VEGF decreased significantly.